tbuckley/cabot-search huggingface dataset:
Imaging Diagnosis of Various Hepatocellular Carcinoma Subtypes and Its Hypervascular Mimics: Differential Diagnosis Based on Conventional Interpretation and Artificial Intelligence
Authors: Yasunori Minami, Naoshi Nishida, Masatoshi Kudo
Journal: Liver Cancer (2022)

Background: Hepatocellular carcinoma (HCC) is unique among malignancies, and its characteristics on contrast imaging modalities allow for a highly accurate diagnosis. The radiological differentiation of focal liver lesions is playing an increasingly important role, and the Liver Imaging Reporting and Data System adopts a combination of major features including arterial phase hyper-enhancement (APHE) and the washout pattern. Summary: Specific HCCs such as well or poorly differentiated type, subtypes including fibrolamellar or sarcomatoid and combined hepatocellular-cholangiocarcinoma do not often demonstrate APHE and washout appearance. Meanwhile, hypervascular liver metastases and hypervascular intrahepatic cholangiocarcinoma can demonstrate APHE and washout. There are still other hypervascular malignant liver tumors (i.e., angiosarcoma, epithelioid hemangioendothelioma) and hypervascular benign liver lesions (i.e., adenoma, focal nodular hyperplasia, angiomyolipoma, flash filling hemangioma, reactive lymphoid hyperplasia, inflammatory lesion, arterioportal shunt), which need to be distinguished from HCC. When a patient has chronic liver disease, differential diagnosis of hypervascular liver lesions can be even more complicated. Meanwhile, artificial intelligence (AI) in medicine has been widely explored, and recent advancement in the field of deep learning has provided promising performance for the analysis of medical images, especially radiological imaging data contain diagnostic, prognostic, and predictive information which AI can extract. The AI research studies have demonstrated high accuracy (over 90% accuracy) for classifying lesions with typical imaging features from some hepatic lesions. The AI system has a potential to be implemented in clinical routine as decision support tools. However, for the differential diagnosis of many types of hypervascular liver lesions, further large-scale clinical validation is still required. Key Messages: Clinicians should be aware of the histopathological features, imaging characteristics, and differential diagnoses of hypervascular liver lesions to a precise diagnosis and more valuable treatment plan. We need to be familiar with such atypical cases to prevent a diagnostic delay, but AI-based tools also need to learn a large number of typical and atypical cases.
Reply to Fillatre <i>et al.</i> and Li <i>et al.</i>
Authors: Mohd H. Abdul-Aziz, Kiran Shekar, Jason A. Roberts
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Reply to Fillatre, et al. and Li, et al.." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Causal Inference and Ventilator-associated Pneumonia-attributable Mortality in COVID-19: On Painting Bull’s-Eyes and Dotting i’s
Authors: Johan Steen, Johan Decruyenaere
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Causal Inference and VAP-attributable Mortality in COVID-19: On Painting Bulls-Eyes and Dotting i’s." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Antimicrobial Exposure: Do Not Forget the Patient’s Condition Beneath the Extracorporeal Membrane Oxygenation Support!
Authors: Pierre Fillatre, Florian Lemaitre, Nicolas Nesseler, François Legay, Nicolas Massart
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients: PROSPECT II
Authors: Christine Gyldenkerne, Michael Maeng, Lars Kjøller-Hansen, Akiko Maehara, Zhipeng Zhou, Ori Ben-Yehuda, Hans Erik Bøtker, Thomas Engstrøm, Mitsuaki Matsumura, Gary S. Mintz, Ole Fröbert, Jonas Persson, Rune Wiseth, Alf I. Larsen, Lisette O. Jensen, Jan E. Nordrehaug, Øyvind Bleie, Elmir Omerovic, Claes Held, Stefan K. James, Ziad A. Ali, Hans C. Rosen, Gregg W. Stone, David Erlinge
Journal: Circulation (2022)

Background: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content. Methods: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion–related MACEs and high-risk plaque characteristics. Results: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14–3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12–12.77)]) and nonculprit lesion–related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25–6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P =0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P =0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P =0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P =0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21–5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86–1.69]). Conclusions: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02171065.
Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1
Authors: Tsung-Han S. Hsieh, Claudia Cattoglio, Elena Slobodyanyuk, Anders S. Hansen, Xavier Darzacq, Robert Tjian
Journal: Nature Genetics (2022)

It remains unclear why acute depletion of CTCF (CCCTC-binding factor) and cohesin only marginally affects expression of most genes despite substantially perturbing three-dimensional (3D) genome folding at the level of domains and structural loops. To address this conundrum, we used high-resolution Micro-C and nascent transcript profiling in mouse embryonic stem cells. We find that enhancer-promoter (E-P) interactions are largely insensitive to acute (3-h) depletion of CTCF, cohesin or WAPL. YY1 has been proposed as a structural regulator of E-P loops, but acute YY1 depletion also had minimal effects on E-P loops, transcription and 3D genome folding. Strikingly, live-cell, single-molecule imaging revealed that cohesin depletion reduced transcription factor (TF) binding to chromatin. Thus, although CTCF, cohesin, WAPL or YY1 is not required for the short-term maintenance of most E-P interactions and gene expression, our results suggest that cohesin may facilitate TFs to search for and bind their targets more efficiently.
High-flow versus Venturi Mask Oxygen Therapy to Prevent Reintubation: A Matter of Time or Device?
Authors: Mohanchandra Mandal, Dipasri Bhattacharya, Prosenjit Mukherjee, Antonio M. Esquinas
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"High-Flow Versus Venturi Mask Oxygen Therapy to Prevent Re-intubation: A Matter of Time or Device?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Correction: PINK1 Is a Negative Regulator of Growth and the Warburg Effect in Glioblastoma
Authors: Sameer Agnihotri, Brian Golbourn, Xi Huang, Marc Remke, Susan Younger, Rob A. Cairns, Alan Chalil, Christian A. Smith, Stacey-Lynn Krumholtz, Danielle Mackenzie, Patricia Rakopoulos, Vijay Ramaswamy, Michael S. Taccone, Paul S. Mischel, Gregory N. Fuller, Cynthia Hawkins, William Stanford, Michael D. Taylor, Gelareh Zadeh, James T. Rutka
Journal: Cancer Research (2022)

In the original version of this article (1), there was an error in Fig. 2A. Specifically, the incorrect β-actin Western blot image was used. The correct image has been provided, and the error has been corrected in the latest online HTML and PDF version of the article. The authors regret this error.
BI-907828, a novel potent MDM2 inhibitor, inhibits glioblastoma brain tumor stem cells in vitro and prolongs survival in orthotopic xenograft mouse models
Authors: Xiaoguang Hao, Ravinder K Bahia, Orsolya Cseh, Danielle A Bozek, Sophia Blake, Jörg Rinnenthal, Ulrike Weyer-Czernilofsky, Dorothea Rudolph, H Artee Luchman
Journal: Neuro-Oncology (2022)

The tumor suppressor TP53 (p53) is frequently mutated, and its downstream effectors inactivated in many cancers, including glioblastoma (GBM). In tumors with wild-type status, p53 function is frequently attenuated by alternate mechanisms including amplification and overexpression of its key negative regulator, MDM2. We investigated the efficacy of the MDM2 inhibitor, BI-907828, in GBM patient-derived brain tumor stem cells (BTSCs) with different amplification statuses of MDM2, in vitro and in orthotopic xenograft models.In vitro growth inhibition and on-target efficacy of BI-907828 were assessed by cell viability, co-immunoprecipitation assays, and western blotting. In vivo efficacy of BI-907828 treatments was assessed with qPCR, immunohistochemistry, and in intracranial xenograft models.BI-907828 decreases viability and induces cell death at picomolar concentrations in both MDM2 amplified and normal copy number TP53 wild-type BTSC lines. Restoration of p53 activity, including robust p21 expression and apoptosis induction, was observed in TP53 wild-type but not in TP53 mutant BTSCs. shRNA-mediated knock-down of TP53 in wild-type BTSCs abrogated the effect of BI-907828, confirming the specificity of the inhibitor. Pharmacokinetic-pharmacodynamic studies in orthotopic tumor-bearing severe combined immunodeficiency (SCID) mice demonstrated that a single 50 mg/kg p.o. dose of BI-907828 resulted in strong activation of p53 target genes p21 and MIC1. Long-term weekly or bi-weekly treatment with BI-907828 in orthotopic BTSC xenograft models was well-tolerated and improved survival both as a single-agent and in combination with temozolomide, with dose-dependent efficacy observed in the MDM2 amplified model.BI-907828 provides a promising new therapeutic option for patients with TP53 wild-type primary brain tumors.
Elevated Childhood Insulin-related Asthma Is a Risk Factor for Reduced Lung Function
Authors: Tara F. Carr, Debra A. Stern, Wayne Morgan, Stefano Guerra, Fernando D. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Elevated Childhood Insulin-related Asthma Is Risk Factor for Reduced Lung Function." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
HNF1B Alters an Evolutionarily Conserved Nephrogenic Program of Target Genes
Authors: Kelli Grand, Martine Stoltz, Ludovica Rizzo, Ruth Röck, Michael M. Kaminski, Gabriela Salinas, Maike Getwan, Thomas Naert, Roman Pichler, Soeren S. Lienkamp
Journal: Journal of the American Society of Nephrology (2022)

Background Hepatocyte nuclear factor-1 beta (HNF1B) is an essential transcription factor during embryogenesis. Mutations in HNF1B are the most common monogenic causes of congenital cystic dysplastic renal malformations. The direct functional consequences of mutations in HNF1B on its transcriptional activity are unknown. Methods Direct reprogramming of mouse fibroblasts to induced renal tubular epithelial cells was conducted both with wild-type HNF1B and with patient mutations. HNF1B was expressed in Xenopus ectodermal explants. Transcriptomic analysis by bulk RNA-Seq identified conserved targets with differentially regulated expression by the wild-type or R295C mutant. CRISPR/Cas9 genome editing in Xenopus embryos evaluated transcriptional targets in vivo . Results HNF1B is essential for reprogramming mouse fibroblasts to induced renal tubular epithelial cells and induces development of ectopic renal organoids from pluripotent Xenopus cells. The mutation R295C retains reprogramming and inductive capacity but alters the expression of specific sets of downstream target genes instead of diminishing overall transcriptional activity of HNF1B. Surprisingly, targets associated with polycystic kidney disease were less affected than genes affected in congenital renal anomalies. Cross-species–conserved transcriptional targets were dysregulated in hnf1b CRISPR-depleted Xenopus embryos, confirming their dependence on hnf1b . Conclusions HNF1B activates an evolutionarily conserved program of target genes that disease-causing mutations selectively disrupt. These findings provide insights into the renal transcriptional network that controls nephrogenesis.
Disinhibition of the orbitofrontal cortex biases decision-making in obesity
Authors: Lauren T. Seabrook, Lindsay Naef, Corey Baimel, Allap K. Judge, Tyra Kenney, Madelyn Ellis, Temoor Tayyab, Mataea Armstrong, Min Qiao, Stan B. Floresco, Stephanie L. Borgland
Journal: Nature Neuroscience (2022)
Wildfires and the Changing Landscape of Air Pollution–related Health Burden in California
Authors: Ruwan Thilakaratne, Sumi Hoshiko, Andrew Rosenberg, Thomas Hayashi, Joseph Ryan Buckman, Ana G. Rappold
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Wildfires are a growing source of pollution including particulate matter ⩽2.5 μm in aerodynamic diameter (PM2.5), but associated trends in health burden are not well characterized. Objectives: We investigated trends and disparities in PM2.5-related cardiorespiratory health burden (asthma, chronic obstructive pulmonary disease, and all-cause respiratory and cardiovascular emergency department [ED] visits and hospital admissions) for all days and wildfire smoke-affected days across California from 2008 to 2016. Methods: Using residential Zone Improvement Plan code and daily PM2.5 exposures, we estimated overall and subgroup-specific (age, gender, race and ethnicity) associations with cardiorespiratory outcomes. Health burden trends and disparities were evaluated on the basis of relative risk, attributable number, and attributable fraction by demographic and geographic factors and over time. Measurements and Main Results: PM2.5-attributed burden steadily decreased, whereas the fraction attributed to wildfire smoke varied by fire season intensity, constituting up to 15% of the annual PM2.5-burden. The highest relative risk and PM2.5-attributed burden (92 per 100,000 people) was observed for respiratory ED visits, accounting for 2.2% of the respiratory annual burden. Disparities in overall morbidity in the oldest age, Black, and “other” race groups were also reflected in PM2.5-attributed burden, whereas Asian populations had the highest risk rate in respiratory outcomes and thus the largest fraction of the total burden attributed to the exposure. In contrast, high wildfire PM2.5-attributed burden rates in rural, central, and northern California populations occurred because of differential exposure. Conclusions: In California, wildfires’ impact on air quality offset the public health gains achieved through reductions in nonsmoke PM2.5. Disproportionate effects could be attributed to differences in subpopulation susceptibility, relative risk, and differential exposure.
The evolution of peace
Authors: Luke Glowacki
Journal: Behavioral and Brain Sciences (2022)

Abstract While some species have affiliative and even cooperative interactions between individuals of different social groups, humans are alone in having durable, positive-sum, interdependent relationships across unrelated social groups. Our capacity to have harmonious relationships that cross group boundaries is an important aspect of our species' success, allowing for the exchange of ideas, materials, and ultimately enabling cumulative cultural evolution. Knowledge about the conditions required for peaceful intergroup relationships is critical for understanding the success of our species and building a more peaceful world. How do humans create harmonious relationships across group boundaries and when did this capacity emerge in the human lineage? Answering these questions involves considering the costs and benefits of intergroup cooperation and aggression, for oneself, one's group, and one's neighbor. Taking a game theoretical perspective provides new insights into the difficulties of removing the threat of war and reveals an ironic logic to peace – the factors that enable peace also facilitate the increased scale and destructiveness of conflict. In what follows, I explore the conditions required for peace, why they are so difficult to achieve, and when we expect peace to have emerged in the human lineage. I argue that intergroup cooperation was an important component of human relationships and a selective force in our species history beginning at least 300 thousand years. But the preconditions for peace only emerged in the past 100 thousand years and likely coexisted with intermittent intergroup violence which would have also been an important and selective force in our species' history.
Author Correction: Learning to distinguish progressive and non-progressive ductal carcinoma in situ
Authors: Anna K. Casasent, Mathilde M. Almekinders, Charlotta Mulder, Proteeti Bhattacharjee, Deborah Collyar, Alastair M. Thompson, Jos Jonkers, Esther H. Lips, Jacco van Rheenen, E. Shelley Hwang, Serena Nik-Zainal, Nicholas E. Navin, Jelle Wesseling, Elinor J. Sawyer, Helen R. Davies, Andrew Futreal, Nicholas E. Navin, E. Shelley Hwang, Jacco van Rheenen, Fariba Behbod, Marjanka Schmidt, Lodewyk F. A. Wessels, Daniel Rea, Hilary Stobart, Donna Pinto, Ellen Verschuur, Marja van Oirsouw
Journal: Nature reviews. Cancer (2022)
Serotonin regulation of behavior via large-scale neuromodulation of serotonin receptor networks
Authors: Piergiorgio Salvan, Madalena Fonseca, Anderson M. Winkler, Antoine Beauchamp, Jason P. Lerch, Heidi Johansen-Berg
Journal: Nature Neuroscience (2022)

Abstract Although we understand how serotonin receptors function at the single-cell level, what role different serotonin receptors play in regulating brain-wide activity and, in turn, human behavior, remains unknown. Here, we developed transcriptomic–neuroimaging mapping to characterize brain-wide functional signatures associated with specific serotonin receptors: serotonin receptor networks (SRNs). Probing SRNs with optogenetics–functional magnetic resonance imaging (MRI) and pharmacology in mice, we show that activation of dorsal raphe serotonin neurons differentially modulates the amplitude and functional connectivity of different SRNs, showing that receptors’ spatial distributions can confer specificity not only at the local, but also at the brain-wide, network level. In humans, using resting-state functional MRI, SRNs replicate established divisions of serotonin effects on impulsivity and negative biases. These results provide compelling evidence that heterogeneous brain-wide distributions of different serotonin receptor types may underpin behaviorally distinct modes of serotonin regulation. This suggests that serotonin neurons may regulate multiple aspects of human behavior via modulation of large-scale receptor networks.
Early rhythm-control therapy for atrial fibrillation in patients with a history of stroke: a subgroup analysis of the EAST-AFNET 4 trial
Authors: Märit Jensen, Anna Suling, Andreas Metzner, Renate B Schnabel, Katrin Borof, Andreas Goette, Karl Georg Haeusler, Antonia Zapf, Karl Wegscheider, Larissa Fabritz, Hans-Christoph Diener, Götz Thomalla, Paulus Kirchhof
Journal: The Lancet Neurology (2022)
Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study
Authors: Bijal D. Shah, Armin Ghobadi, Olalekan O. Oluwole, Aaron C. Logan, Nicolas Boissel, Ryan D. Cassaday, Thibaut Leguay, Michael R. Bishop, Max S. Topp, Dimitrios Tzachanis, Kristen M. O’Dwyer, Martha L. Arellano, Yi Lin, Maria R. Baer, Gary J. Schiller, Jae H. Park, Marion Subklewe, Mehrdad Abedi, Monique C. Minnema, William G. Wierda, Daniel J. DeAngelo, Patrick Stiff, Deepa Jeyakumar, Jinghui Dong, Sabina Adhikary, Lang Zhou, Petra C. Schuberth, Imi Faghmous, Behzad Kharabi Masouleh, Roch Houot
Journal: Journal of Hematology & Oncology (2022)

Abstract Background Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 CAR T-cell therapy approved in the USA to treat adult patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (R/R B-ALL) based on ZUMA-3 study results. We report updated ZUMA-3 outcomes with longer follow-up and an extended data set along with contextualization of outcomes to historical standard of care. Methods Adults with R/R B-ALL received a single infusion of KTE-X19 (1 × 10 6 CAR T cells/kg). Long-term post hoc subgroup assessments of ZUMA-3 were conducted. Outcomes from matched patients between historical clinical trials and ZUMA-3 patients were assessed in the retrospective historical control study SCHOLAR-3. Results After 26.8-months median follow-up, the overall complete remission (CR) rate (CR + CR with incomplete hematological recovery) among treated patients ( N = 55) in phase 2 was 71% (56% CR rate); medians for duration of remission and overall survival (OS) were 14.6 and 25.4 months, respectively. Most patients responded to KTE-X19 regardless of age or baseline bone marrow blast percentage, but less so in patients with &gt; 75% blasts. No new safety signals were observed. Similar outcomes were observed in a pooled analysis of phase 1 and 2 patients ( N = 78). In SCHOLAR-3, the median OS for treated patients from ZUMA-3 ( N = 49) and matched historical controls ( N = 40) was 25.4 and 5.5 months, respectively. Conclusions These data, representing the longest follow-up of CAR T-cell therapy in a multicenter study of adult R/R B-ALL, suggest that KTE-X19 provides a clinically meaningful survival benefit with manageable toxicity in this population. Trial Registration : NCT02614066.